European Heart Journal (1996) 17 {Supplement D), 2-8
Risk factors for cardiovascular disease in women:
assessment and management
K. Schenck-Gustafsson
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden
Coronary heart disease (CHD) is the most important
cause of death and disability among older women. A
50-year-old woman has a 46% risk of having CHD and a
31% risk of dying from it. Female CHD patients have a
distinct clinical presentation, which includes more severe
thromboembolic disease without coronary arteriosclerosis.
Syndrome X also appears to be more prevalent in women.
Oestrogen deficiency may be a trigger for this syndrome.
The magnitude of the effect of various risk factors may
also differ between women and men. In addition, there
are risk factors unique to women. Lipid profiles differ
between men and women. After menopause, the lipid
profile changes unfavourably, with increasing levels of
LDL cholesterol and decreasing levels of HDL choles-
terol. Cigarette smoking, hypertension, diabetes mellitus,
Introduction
Coronary heart disease (CHD) is the leading cause of
death and disability among older women. In Sweden it is
the main cause of death for women over the age of 55
years and for men over the age of 45 years1'1, and in the
United States it is the primary cause of death among
women over the age of 60 years. In this age group, one
in four women, as well as one in four men, die of
CHD[21. The rates of mortality from CHD have been
falling since the 1960s, but in the United States the rate
of decline has been slower among women than among
men since 1979'31. In Sweden, the decline in the mortality
rate for women is also slower than for men, although the
change came later1'1. The decline in mortality rates for
women was reduced by 20% and for men by 30%,
leading to a reduction in gender differences in mortality
from myocardial infarction (MI)111.
France has the lowest mortality from MI in
Europe (21/100 000), and other Mediterranean countries
also have low mortality rates. The United Kingdom,
Ireland, Hungary, Poland, Russia, and other eastern
European countries have the highest incidence of death
Correspondence- Dr Karin Schenck-Gustafsson, Associate
Professor, Department of Cardiology, Karolinska Hospital, Box
110, Stockholm, Sweden, S-171 76.
0195-668X/96/0DO002+07 $18.00/0
and obesity are all recognised risk factors for CHD in
women.
It is important to recognise that risk factors for CHD differ
between men and women. Advising women to quit cigarette
smoking, avoid obesity, increase physical activity, and
prevent and treat hypertension and hyperlipidaemia will
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result in a reduction in CHD risk. Additional studies are
needed to further contribute to our understanding of the
complex risk factors underlying the development of CHD
in women.
(Eur Heart J 1996; 17 (Suppl D): 2-8)
Key Words: Coronary artery disease (CAD), risk factors,
oestrogen replacement therapy, oestrogen.
from cardiovascular diseases in Europe'4'. A 50-year-old
woman has a 46% risk of having CHD during the rest of
her life and a 31% risk of dying of CHD. In comparison,
her chances of having or dying of breast cancer are 10%
and 3% respectively, and her chances of having or dying
of a hip fracture are 15% and 1-5% respectively151.
Clinical presentation and assessment
The Framingham Study reported that more women than
men have angina pectoris as their initial symptom of
CHD (65% vs 35%), while fewer women than men (29%
vs 43% ) suffer an MI as their first manifestation'6'. The
Framingham Study reported that women are more
likely than men to experience an unrecognized, or silent
MI, which would later be diagnosed during a routine
examination'61. Women may also delay seeking medical
attention if they suspect an MI. MI is more often fatal in
women than in men'71, and, in fact, 36% of women
who die of coronary artery disease present with sudden
cardiac death or MI161. Interestingly, women with
recurrent silent MI have an increased overall mor-
tality*81. Women are usually seven to ten years older than
men at the time they experience an MI, so the symptoms
may result from age rather than gender171. MI occurs
with more seasonal variation in women than in
1996 The European Society of Cardiology

men, with an increase in incidence in the autumn and
winter191.
Women presenting with an acute infarction have
the same weekly number of episodes, precipitants of
angina, and frequency of angina at rest as do men'101.
Presenting symptoms in both men and women include
chest pain with typical radiation, nausea, and dia-
phoresis, but men are more likely than women to present
initially with ventricular tachycardia'71.
Electrocardiographic changes detected with vec-
tor analysis during the first 24 h after MI differ between
men and women. Women have fewer ST-elevations
during an acute MI[11', which might explain why women
experience less thrombolysis in connection with MI than
men. The same is seen during PTCA (percutaneous
transluminal coronary angioplasty). Women probably
have less advanced coronary stenosis than men at the
time of infarction'121, and it is postulated, but not really
proven, that women have more non-Q infarctions.
Mechanical complications associated with MI occur
more in women, possibly because women have less
collateral vessel development, and tend to be older and
have more advanced disease than men'131.
Women are less likely than men to be referred for
coronary angiography114"171, but the results of angio-
grams are interesting. After MI, women more often have
normal findings in coronary angiograms than do men,
and also have less collateral vessel development'181.
More than 50% of women with angina pectoris under-
going coronary angiography have normal arteries,
compared with 16% of men'191.
A review of the angiographic findings in
almost 5000 patients showed that women with atypical
angina pectoris seldom have coronary artery disease1201.
According to this report, a 45-year-old woman with
atypical angina pectoris has a 13% chance of having
CHD. These calculations are based only on sex and age;
however, and if other risk factors are considered, like
hypertension, hyperlipidaemia, diabetes mellitus, and
resting electrocardiogram with ST-T wave changes, the
likelihood of coronary artery disease occurring would be
higher. The fact that prior epidemiological studies have
been conducted in predominantly male populations
makes it difficult to estimate the likelihood of CHD in
women.
Coronary angiography may not be the best
method for diagnosing coronary artery disease. New
techniques like intravascular ultrasound and magnetic
resonance imaging detect atheromatosis in spite of
apparently normal coronary angiography results.
Syndrome X, which is angina pectoris and positive
exercise-related ECG changes in the presence of normal
coronary angiograms, appears to be more prevalent in
women than in men. It is related to menopause, with an
overall imbalance in vasomotor tone in all vessels
including the coronaries, and oestrogen deficiency may
be a trigger.
Non-invasive diagnostic testing of coronary
artery disease in women has less predictive value than it
does in men. A study performed in 1975 reported an
Risk factors in women 3
incidence of true-positive exercise tests of 89% in men
and 33% in women, using positive coronary angiograms
as a comparison'2'1. False-positive results were 8% for
men and 67% for women. Thus, a positive exercise test is
of little value in predicting the presence of significant
coronary artery disease in women. This result was
confirmed in several later studies, including one from
our own group1221. Rate-pressure product and exer-
cise capacity may be the best diagnostic parameters
in women'231. Stress radionuclide ventriculography
performed in women with coronary artery disease
appears to demonstrate left ventricular dysfunction
during exercise, but the poor specificity of the exercise
ejection fraction in females may limit the diagnostic
applicability of this test. Stress ECG combined with
technetium scintigraphy provides both the sensitivity
and specificity required for diagnosis in women'241. Scan
interpretation may be complicated because breast tissue
attenuates myocardial activity, resulting in defects in the
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anterior and septal distributions. The shifting of breast
tissue may lead one to conclude that redistribution has
occurred'251. Gender-matched normal databases should
be constructed for quantitative scan analysis'261.
Risk factors
The magnitude of the effects of various risk factors for
coronary heart disease may be different in men and
women, and there are risk factors that are unique to
women. Conclusions drawn from studies performed only
on men cannot, therefore, be extrapolated to women.
Lipoproteins
Most lipid-lowering trials have involved only men.
Because the lipid profile differs between men and women
and the life patterns of lipoprotein levels are different, it
is difficult to determine if the results of these trials
pertain to women.
Before menopause, low-density lipoprotein
(LDL) cholesterol levels are lower in women than in
men. After menopause, the LDL cholesterol levels
increase to levels greater than those in men. Triglyceride
levels and a lipoprotein a particle (LPa) also increase,
and high-density lipoprotein (HDL) cholesterol levels
decrease after menopause. HDL cholesterol levels are
higher in women than in men'271, however, over the
entire life span. The increase in LDL cholesterol levels
after menopause might be caused by decreased LDL
receptor activity. The enzyme hepatic lipase decreases
also, with decreasing oestrogen levels, which might be
important for HDL cholesterol concentrations. The
increase in LDL cholesterol levels after menopause
might be caused by decreased LDL receptor activity.
A direct antioxidant effect on LDL cholesterol
has also been reported with 17 /?-oestradiol'28]. Oestro-
gen for post-menopausal women may act in a manner
similar to the statins, a new class of lipid-lowering drugs.
Eur Heart J, Vol. 17, Suppl D 1996
4 K. Schenck-Gustafsson
Primary prevention and lipoproteins in
women
The results of epidemiological studies suggest that
elevated total cholesterol and triglycerides predict CHD
among middle-aged and older women129'301. High tri-
glyceride levels (often associated with lifestyle factors
like obesity, stress, and alcohol intake) are even better
predictors for CHD in women, and are often related to
the HDL cholesterol fraction. LDL cholesterol levels
appear to be less important in diagnosing CHD in
younger women, but for older women as well as for men,
LDL levels are a powerful predictor of MI13'1. As well as
age, another important factor in evaluating the risk
associated with an elevated LDL concentration is the
number of years since menopause.
Data on primary prevention of CHD by modifi-
cation of the lipid profile in healthy women are limited.
It is still unclear whether healthy women with modestly
raised cholesterol levels benefit from lipid-lowering
interventions. If such an intervention is undertaken, the
aim should be to raise HDL cholesterol levels and lower
LDL cholesterol levels, similar to how oestrogens func-
tion. In the U.S.A. the Women's Health Initiative
(WHI) is studying 60 000 women to evaluate, among
other things, the effect of lipid-lowering interventions on
healthy women.
Secondary prevention and lipoproteins in
women
Few secondary prevention intervention trials have
included women at all, or in large enough numbers to
provide significant information. In one trial including
over 7000 women'321, however, lovastatin was tested and
no gender difference was found in its effects on LDL
cholesterol, triglyceride, or HDL cholesterol levels. The
only trial that had hard end-points like mortality,
reinfarction, and cardiovascular events in a lipid-
lowering trial was the 4 S study1331. This study included
about 700 women who had had MI or angina pectoris;
this number was too small to show a reduction in total
mortality. A clear reduction was found in reinfarction
and coronary artery disease events in women.
The results of these studies suggest that women
with hypercholesterolaemia after a MI should change
their eating habits and be treated with lipid-lowering
drugs to lower their cholesterol levels. A low-fat/
cholesterol diet alone may be more beneficial for men
than for women'341, however.
Cigarette smoking
Smoking is more common among younger women than
younger men in most western countries, and it is an
increasing health problem. Adult women have not quit
smoking at the same rate as men, probably because they
Eur Heart J, Vol. 17, Suppl D 1996
fear gaining weight. The number of women who start to
smoke in their teenage years and continue to smoke
throughout adult life is, therefore, increasing. At the
present time, peri-menopausal women form the first
cohort of women ever with a lifetime history of cigarette
smoking comparable with the male cohorts. Cigarette
smoking alters the oestrogen metabolism in pre- and
post-menopausal women135"371. The resulting lower
oestrogen levels cause a premature menopause, which
increases the risks of CHD. Increased coronary heart
disease and adverse lipid profiles have been demon-
strated in middle-aged women who smoke cigarettes'381.
Women who are heavy smokers (>20 cigarettes daily)
have a much greater risk of CHD than do women who
do not smoke1391. Even female 'light smokers' (1-4
cigarettes daily) have more than twice the risk of
coronary artery disease than non-smokers1401. Passive
smoking and smoking 'low-yield' cigarettes (reduced tar,
nicotine, and carbon monoxide) are also dangerous
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for women. Among healthy women, the progression
of aortic calcification correlates with the number of
cigarettes smoked daily. Quitting smoking after many
years will reduce, but not eliminate, the risk of aortic
calcification14'1.
Because of the high prevalence of smoking
among women, reducing cigarette smoking will prob-
ably be the single most effective measure to prevent
CHD on a population basis137'391.
Hypertension
Until about 20 years ago it was generally accepted that
women, especially older women, tolerate higher blood
pressure and that hypertension in this group should not
be treated. More recently, however, several studies have
shown a strong association between elevated blood
pressure and CHD in women142^*3'. Isolated systolic
hypertension is more prevalent among older women
with loss of arterial elasticity (approximately 30%
of women over 65 years), and these women have an
elevated risk of death from stroke or coronary heart
disease.
Early menopause is associated with an increase
in diastolic blood pressure. Oestrogen therapy generally
reduces the blood pressure of post-menopausal women,
particularly for women whose initial blood pressure is
slightly elevated. It has been debated whether or not to
treat mild-to-moderate hypertension (i.e. diastolic BP
between 90 and 114 mmHg). A meta-analysis of rand-
omized drug treatment trials evaluated therapy for mild-
to-moderate hypertension. These trials involved 37 000
subjects, 47% of whom were women. The meta-analysis
showed that a mean decrease of 6 mmHg in diastolic
pressure significantly reduced overall mortality from
vascular disease by 21%, stroke by 42%, and coronary
heart disease by 14%146]. Hypertension studies conducted
in Europe and the United States involving over 13 000
women reported a decrease in all causes of mortality
among treated vs control women, but these trials

were not designed to examine mortality in women
specifically147-481.
Three large hypertension trials including a large
number of women have shown the benefits of therapy,
with even better results of blood pressure lowering in
older women than in men. The results of these trials
showed significant reduction in death from stroke and
coronary-related events in patients up to 84 years of age
with either mixed or isolated systolic hypertension'49"5''.
In the Nordic countries, hypertensive women
receive diuretics, especially thiazide diuretics, much
more than do hypertensive men. In spite of being the
cheapest hypertensive drug, it might be unsuitable
for women because it increases cholesterol levels, and
LDL cholesterol levels rise markedly with age in
post-menopausal women.
In conclusion, we know very little about the
interactions between hormone replacement therapy and
different antihypertensive agents. Oestrogens may act
like calcium channel blockers, suggesting that a possible
synergistic effect with other hypertensive drugs may be
possible.
Diabetes mellitus
The incidence of diabetes mellitus in women increases
manyfold after menopause. The disease process in
diabetes may impair oestrogen binding and counteract
the protection against CHD that endogenous oestrogen
confers on premenopausal women. Diabetes may also
exacerbate the effects of known coronary risk factors in
women. Diabetic women have a higher mortality and
morbidity rate from CHD than diabetic men'52"54',
which suggests that sex hormones influence glucose and
insulin metabolism.
Impaired glucose tolerance is predictive of CHD,
and the increased risk is likely to be mediated through
insulin resistance and hyperinsulinaemia. Insulin resist-
ance induces adverse changes in lipids and lipoproteins
and may be of special importance in female patients
with syndrome X (typical angina pectoris, pathological
exercise test, and angiographically smooth coronary
arteries on the coronary angiogram). Oestrogens
may affect glucose tolerance in a positive way and be
important for female patients with syndrome X.
Three percent of pregnant women develop
gestational diabetes, and this may be a marker for
increased risk of CHD. About one-third of these women
will later develop non-insulin dependent diabetes
mellitus, and also hypertension, adverse lipid profiles,
and abnormal electrocardiograms.
Obesity and body fat distribution
Obesity increases the risk of coronary heart disease. A
woman with a body-mass index (the weight in kilograms
divided by the square of the height in meters) of 29 or
higher has three times the risk that a lean woman has1551.
Risk factors in women
A large part of the increase in risk is attributable to the
influence of adiposity on blood pressure, glucose
tolerance, and lipid levels. After adjustment for these
variables, a moderate residual effect persists. Women
who maintain an ideal body weight have a 3560% lower
risk of MI than women who become obese, according to
the Framingham Study data'5*1.
In women, there are interrelationships among
body fat, oestrogen synthesis, and lipoprotein metab-
olism. Obese women have higher oestrone levels in
adipose tissue. Oestrone is less active compared to
oestradiol, but it still plays a role. Obese women reach
menopause later than lean women, which provides
greater protection against osteoporosis, but also pro-
motes an increased risk of developing endometrial
cancer. These trends indicate that obese and lean women
have different oestrone activities. It is still unclear what
obesity and oestrone levels will mean for the risk of
CHD.
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The type of obesity (android, abdominal, or
central) is an independent risk for cardiovascular disease
in women and also independent of the degree of overall
obesity. The risk for CHD rises among women with a
waist-to-hip ratio higher than 0-8. These women
generally have insulin resistance, reduced HDL
cholesterol levels, hypertriglyceridaemia, hypertension,
and decreased sex hormone-binding globulin levels.
This characteristic is sometimes combined with the
cardiological syndrome X'57>58).
Higher levels of free testosterone have been
found in healthy women with central adiposity com-
pared with women with greater peripheral adiposity1591.
Females with abdominal central fat have elevated
plasminogen-activator-inhibitor-1 antigen and reduced
fibrinolytic potential'601, and tend to smoke cigarettes
and have a more sedentary lifestyle than lean women.
Haemostasis
The majority of the studies investigating the effects of
aspirin on primary prevention were performed on men,
while the evidence for aspirin's effects on women comes
mainly from observational data. Randomized clinical
trials of aspirin use in healthy women are, however,
underway.
The results of the Nurses' Health Study showed
that the incidence of first MI was reduced in women
taking low-dose aspirin and aged 50 years or more,
compared with women reporting no aspirin use. No
protective effect for stroke was seen'6'1. Smaller
experimental studies1621 suggest a sex difference in the
antithrombotic effects of aspirin.
Thrombolytic treatment in acute MI seems to
have the same beneficial effects in both women and men.
Women with MI seemed to have good acute effects from
streptokinase treatment, but the relative reduction in
mortality in the follow-up was less than that of men
in three big studies'63"651. Women also appeared to
derive less benefit from streptokinase, aspirin, or their
Eur Heart J, Vol. 17, Suppl D 1996
6 K. Schenck-Gusiafsson
combination when compared to men in the ISIS-2
study1661. Female patients receiving tPA within 4 h had
greater frequency of death and combined reinfarction
and death in the TIMI study1671. Women with CHD had
higher plasma levels of von Willebrand factor antigen,
PA1-1, and fibrinogen than women in a matched control
group in the Stockholm Study1681. Fibrinogen and LP(a)
have been linked to CHD in women'691. The role of
post-menopausal hormonal replacement therapy and
venous thrombosis and stroke is still unclear, but there
is, so far, no hard evidence of an oestrogen-induced
increased risk.
Physical activity
There is little direct evidence that physical activity
reduces the incidence of coronary heart disease in
women. Moderate levels of exercise appear to result in
reduced weight, blood pressure, and cholesterol levels.
The influence of physical activity on lipid levels in
women differs in pre- vs post-menopausal women. In
post-menopausal women, exercise decreases endogenous
oestrogen concentrations via a reduction in body fat,
and this may lead to unfavourable levels of HDL
cholesterol and LDL cholesterol. Higher endogenous
levels of oestrone are linked to higher HDL cholesterol
and lower LDL cholesterol levels among pre- and
post-menopausal women'701.
Psychosocial risk factors
Psychosocial risk factors differ between men and
women, as shown by Frankenhauser et a/.'7'1 who
studied middle managers at the Swedish Volvo
company. They found that the female managers arriving
home from work had a rise in noradrenaline levels in
urine and an increase in pulse and blood pressure,
compared with male managers.
So far, few studies have included an adequate
number of women to be able to make conclusions
concerning psychosocial risk factors for CHD. The
Stockholm Study on psychosocial risk factors in women
with CHD found that patients were more depressed, had
more signs of vital exhaustion, less ability to cope,
worse quality of life, and worse belief in the future as
compared with matched controls. Type A behaviour and
social support were not important, but low education
and high work stress were important risk factors for
CHD*721.
The role of hormones
One reason why women suffer from CHD 10-15 years
later than men relates to hormone differences. Indirect
evidence for this hypothesis is that premature
menopause and premature oophorectomy consistently
increase the risk for MI in women1731. Most epidemio-
Eur Heart J, Vol. 17, Suppl D 1996
logical studies have shown an independent, statistically
significant increased rate of CHD among women with
more and/or earlier reproductive events'74'. The decreas-
ing levels of oestrogens with age and the concomitant
increased LDL cholesterol level are natural, unique risk
factors for female patients. The ten-year gap in develop-
ment of cardiovascular disease between older men and
older women is also due to a decelerated increase in the
rate of mortality for coronary heart disease and to
earlier mortality among men. Postmenopausal oestrogen
replacement apparently protects against CHD in
women, partly through its beneficial effects on lipid
levels and on vasculature and endothelial function.
Management
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It is important to recognise that risk factors for coronary
heart disease in women differ from those in men. It is
clear that advising women to quit cigarette smoking,
avoid obesity, and increase physical activity, as well as
to prevent and treat hypertension and hyperlipidaemia,
will result in a reduction in the risk of coronary disease.
Stress management will probably be of great importance
for women also, but more studies need to be performed
in this area.
References
[I] SOS-rapport 1994:4 (Folkhalsorapport 1994).
[2] National Center for Health Statistics of the USA, 1989, vol 2
Mortality, part 1, Washington DC. Government Printing
Office 1993 (DHHS publication number (PHS) 93-1101).
[3] Higgins M, Tom T. Trends in coronary heart disease in the
USA Int J Epidemiol 1989; 19 Suppl I: S58-S66.
[4] WHO, World Health Statistics Annual 1992.
[5] Grady D, Rubin SM, Pettitti DB el al. Hormone therapy to
prevent disease and prolong life in postmenopausal women.
Ann Intern Med 1992; 117: 1016-37.
[6] Lerner DJ, Kannel WB. Patterns of coronary heart disease
morbidity and mortality in the sexes: a 26-year follow-up of
the Framingham population. Am Heart J 1986; 111: 383-90.
[7] Greenland P, Reicher Reiss H, Goodhourt U et al. In-hospital
and 1-year mortality in 1,524 women after myocardial
infarction comparison with 4,315 men. Circulation 1991;
83:484-91.
[8] Kannel WB, Abbott RD. Incidence and prognosis of unrec-
ognized myocardial infarction. An update of the Framingham
Study. N Engl J Med 1984; 311: 1144-7.
[9] Bengtsson C. Ischaemic heart disease in women. Acta Med
Scand 1973; 548 (Suppl): 1S-128S.
[10] Steingart RM, Packer M, Hamn P et al. Sex difference in the
management of coronary artery disease. N Engl J Med 1991;
325: 226-30.
[11] Dellborg M, Swedberg K. Acute myocardial infarction:
difference in the treatment between men and women. Qual
Assur Health Care 1993; 5: 261-5.
[12] Krumholtz HM, Douglas PS, Lauer MS et al. Selection of
patients for coronary angiography and coronary revascular-
ization early after myocardial infarction: is there evidence for
a gender bias? Ann Intern Med 1992; 116: 785-90.
[13] Dellborg M, Held P, Swedberg K el al. Rupture of the
myocardium: occurrence in risk factors. Br Heart J 1985; 54:
11-6.

[14] Tibia JN, Wassertheil-Smoller S, Wexter JP et al. Sex bias in
considering coronary bypass surgery. Ann Intern Med 1987;
107: 19-25.
[15] Ayanian JZ, Epstein AM. Differences in the use of procedures
between women and men hospitalized for coronary heart
disease. N Engl J Med 1991; 325: 221-5.
[16] Steingart RM, Packer M, Hamm P et al. Sex differences in the
management of coronary artery disease. N Engl J Med 1991;
325: 226-30.
[17] Khan SS, Nessim S, Gray R et al. Increased mortality of
women in coronary artery bypass surgery: evidence for a
referral bias. Ann Intern Med 1990; 112: 561-7.
[18] Johansson S, Bergstrand R, Schlossman D et al. Sex
differences in cardioangiographic findings after myocardial
infarction. Eur Heart J 1984; 5: 374-81.
[19] Wenger NO. Gender, coronary artery disease, and coronary
bypass surgery. Ann Intern Med 1990; 112: 557-8.
[20] Diamond GA, Forrester JS. Analysis of probability as an aid
in the clinical diagnosis of coronary artery disease. N Engl J
Med 1979; 300: 1350-8.
[21] Sketch NH, Mohiuddin SM, Lynch JD et al. Significant sex
differences in the correlation of electrocardiographic exercise
testing and coronary arteriograms. Am J Cardiol 1975; 36:
169-73.
[22] Schenck-Gustafsson K, Svane B, Eriksson M, Orth-Gomer K.
Coronary angiograms and other baseline characteristics from
the Stockholm Study of women with coronary artery disease.
Third International Conference on Preventive Cardiology;
June 1993: 125.
[23] Swahn E, Andren B, Nielsen N et al. The usefulness of
pre-discharge exercise test in women with unstable coronary
artery disease. Eur Heart J 1995; 16: 1295.
[24] Friedman D, Green AC, Ishandrian DS et al. Exercise
thallium-201 myocardial scintigraphy in women. Correlation
with coronary arteriography. Am J Cardiol 1982; 49: 1623.
[25] Obsakken MD. Exercise stress testing in women; diagnostic
dilemma. In: Douglas PD, Brest AN, eds. Heart disease in
women. Philadelphia: Davis, 1989: 187-94.
[26] Eisner RL, Tamas MJ, Cloninger H et al. Normal SPECT
thallium-201 bulls eye display, gender differences. J Nucl Med
1988; 29: 1901-9.
[27] National Cholesterol Education Program Second report of
the expert panel on detection, evaluation, and treatment of
high blood cholesterol in adults. Bethesda (MD): National
Institutes of Health, National Heart, Lung and Blood Insti-
tute; 1993 Sept. Report No.: NIH-NHLBI-93-3095 A 4-5.
[28] Sack MN, Rader DJ, Canon RO. Oestrogen and inhibition of
the LDL in postmenopausal women. Lancet 1994; 29: 269-70.
[29] Rossouw WJF. International trials. Proceedings of the
Conference on Cholesterol and Heart Disease in Older
Persons and in Women; 1990 June; Bethesda. National Heart,
Lung and Blood Institute, MH, 1990.
[30] Bengtsson C, Bjorkelund C, Lapidus L, Lissner L.
Associations of serum lipid concentrations and obesity with
mortality in women: 20-year follow-up of participants in
prospective population study in Gothenburg, Sweden. Br Med
J 1993; 307: 1385-8.
[31] Zimetbaum P, Frisham WH, Osi WL el al. Plasma lipids and
lipoproteins and the incidence of cardiovascular disease in the
very elderly. The Bronx Aging Study. Arterioscler Thromb
Vase Biol 1992; 12:416-23.
[32] Shear CL, Franklin FA, Stinnatt S el al. Expanded clinical
evaluation of Lovastatin (EXCEL) Study results. Circulation
1991; 85: 1293-303.
[33] The 4S-Study Group. Randomized trial of cholesterol
lowering in 4,444 patients with coronary heart disease. The
Scandinavian simvastatin survival (4S). Lancet 1994; 344:
1383-9.
[34] Ferro-Luzzi A, Strazzullo P, Scaccini C et al. Changing the
Mediterranean diet: effects on blood lipids. Am J Clin Nutr
1984; 40: 1027-37.
Risk factors in women
[35] Michnovicz JJ, Hershcopf RJ, Nagauma H et al. Increased
2-hydroxylation of oestradiol as a possible mechanism for the
antioestrogenic effect of cigarette smoking. N Engl J Med
1986; 315: 1305-9.
[36] Friedman AJ, Ravnikar VA, Barbieri RL. Serum steroid
hormone profiles in postmenopausal smokers and non
smokers. Fertil Steril 1987; 47: 398-401.
[37] Baron JA, Adams P, Ward M. Cigarette smoking and other
correlates of cytologic oestrogen effect in postmenopausal
women. Fertil Stenl 1988; 50: 766-71.
[38] Meilahn EN, Kuller CH, Stein EA et al. Characteristics
associated with apoprotein and lipoprotein lipid levels in
middle-aged women. Arteriosclerosis 1988; 8: 515-20.
[39] Reducing the health consequences of smoking. Twenty-five
years of progress: a report of the Surgeon General. Rockville
(MD): Department of Health and Human Services; 1989
Report No.: DHHS-CDC-89-8411
[40] Willett WC, Green A, Stampfer MJ et al. Relative and
absolute excess of risks of coronary heart disease among
women who smoke cigarettes. N Engl J Med 1987; 317:
1303-9.
[41] Witteman JCM, Grobbee DE, Valhenburg HA et al. Cigarette
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on October 10, 2016
smoking and the development and progression of aortic
atherosclerosis. Circulation 1993; 88: 2156-62.
[42] Kannel WB, McGee D, Gordon T. A general cardiovascular
nsk profile: the Framingham Study. Am J Cardiol 1976; 38:
46-51.
[43] Johnson JF, Heinman EF, Heiss G et al. Cardiovascular
disease risk factors and mortality among black women and
white women aged 40-64 years in Evans County, Georgia. Am
J Epidemiol 1986; 123: 209-20.
[44] Sigurdsson JA, Bengtsson C, Lapidus L, Lindquist O,
Rafnsson V. Morbidity and mortality in relation to blood
pressure and antihypertensive treatment. A 12-year follow-up
study of a population sample of Swedish women. Acta Med
Scand 1984; 215: 313-22.
[45] Fiebach NH, Herbert PR, Stampfer MJ et al A prospective
study of high blood pressure and cardiovascular disease in
women. Am J Epidemiol 1989; 130: 646-54.
[46] Collins R, Peto R, MacMahon S et al Blood pressure, stroke,
and cardiovascular heart disease. Part 2, Short-term reduction
in blood pressure: overview of randomized drug trials in the
epidemiology context. Lancet 1990; 338' 827-38.
[47] Medical Research Council Working Party. MRC trial of
treatment of mild hypertension. Principal results. Br Med J
1985; 291: 97-104.
[48] Hypertension and Detection Follow-Up Program (HDFP)
Co-Operative Group. Five-year findings of the Hypertension
Detection and Follow-up Program. Mortality by race, sex,
and age. JAMA 1979; 242: 2572-7.
[49] Report by the Management Committee. The Australian
Therapeutic Trial in Mild Hypertension. Lancet 1980; I:
1261-7.
[50] SHEP Cooperative Research Group. Prevention of stroke
by antihypertensive drug treatment in older persons with
isolated systolic hypertension. Final results of the Systolic
Hypertension in the Elderly Program (SHEP). JAMA 1991;
265: 3235-64.
[51] Dahlof B, Lindholm L, Hansson L et al. Morbidity and
mortality in the Swedish Trial in Old Patients with
Hypertension (STOP-Hypertension). Lancet 1991; 338:
1281-5.
[52] Kannel WB, McGee DC. Diabetes and cardiovascular disease:
the Framingham Study. JAMA 1979; 241: 2035-8.
[53] Manson JE, Colditz GA, Stampfer MJ et al. A prospective
study of maturity-onset diabetes mellitus and risk of coronary
heart disease and stroke in women. Arch Intern Med 1991;
151: 1141-7.
[54] Barrett-Connor E, Wingard DL. Sex differential in
ischemic heart disease mortality in diabetics. A prospec-
tive population-based study. Am J Epidemiol 1983; 118:
489-96.
Eur Heart J, Vol. 17, Suppl D 1996
8 AL Schenck-Gustafsson
[55] Manson JE, Colditz GA, Stampfer MJ et al. A prospective
study of obesity and risk of coronary heart disease in women.
N Engl J Med 1990; 322: 882-9.
[56] Kannel WB. Metabolic risk factors for coronary heart disease
in women: perspectives from the Framingham Study. Am
Heart J 1987; 114:413-9.
[57] Bjorntorp P. The associations between obesity, adipose tissue
distribution, and disease. Acta Med Scand 1988; 723: 121-34.
[58] Lapidus L, Bengtsson C, Larsson B et al. Distribution of
adipose tissue and risk of cardiovascular disease and death:
12-year follow-up of participants in the population study of
women in Gothenburg, Sweden. Br Med J 1984; 289: 1257-61.
[59] De Pergola G, De Mitrio V, Perricc A et al. Influence of free
testosterone on antigen levels of plasminogen activator
inhibitor-1 in premenopausal women with central obesity.
Metabolism 1992; 41: 131^4.
[60] Sundell IB, Nilsson TK, Ranby M et al. Fibrinolytic variables
are related to age, sex, blood pressure, and body build
measurements: a cross-sectional study in Norsjo, Sweden. J
Clin Epidemiol 1989; 42: 719-23.
[61] Manson JE, Stampfer MJ, Colditz GA et al. A prospective
study of aspirin use and primary prevention of cardiovascular
disease in women. JAMA 1991; 266: 521-7.
[62] Spranger M, Aspey BS, Harrison MJG. Sex difference in
antithrombotic effect of aspirin. Stroke 1989; 20: 34-7.
[63] European Working Party. Streptokinase in recent myocardial
infarction: a controlled multicenter trial. Br Med J 1971; iii:
325.
[64] Italian Group for the Study of Streptokinase in Myocardial
Infarction (GISSI). Effectiveness of intravenous thrombolytic
therapy in acute myocardial infarction. Lancet 1986; i:
397^02.
[65] GISSI Study Group. Long-term effects of intravenous
thrombolysis in acute myocardial infarction: final report of
the GISSI Study. Lancet 1987; i: 871-4.
Eur Heart J, Vol. 17, Suppl D 1996
[66] ISIS-2 Collaborative Group. Randomized trial of intravenous
streptokinase, oral aspirin, both, or neither among 17,187
cases of suspected acute myocardial infarction. Lancet 1988; 1:
349-60.
[67] Becker RC, Terrin M, Ross R et al. For the TIM I
Investigators: the TIMI Phase II Experience. Ann Intern Med
1994; 120: 638-^5.
[68] Eriksson M, Schenck-Gustafsson K, Engberg N et al. Von
Willebrand factor antigen and PAI-I as risk factors in women
with coronary artery disease. Thromb Haemost 1993; 69: 455
(Abstr 907).
[69] Meilahn EN. Haemostatic factors and risk of cardiovascular
disease in women: an overview. Arch Pathol Lab Med 1992;
116: 1313-17.
[70] Tyrsler HA, Heyden S, Bartel A et al. Blood pressure and
cholesterol as coronary heart disease risk factors. Arch Intern
Med 1971; 128: 907-14.
[71] Frankenhauser M, Lundberg U, Fredrikson M et al. Stress on
and off the job as related to sex and occupational status in
white-collar workers. Journal of Organizational Behavior
1989; 10: 321^6.
[72] Orth-Gom6r K., Schenck-Gustafsson K, Moser V. Psycho-
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on October 10, 2016
social risk factors for CAD in women. Stress research report
on 255, ISBN 280-2783, National Institute for Psychosocial
Factors and Health, February 1995.
[73] Rosenberg L, Hennekens CH, Rosner B et al. Early
menopause and the risk of myocardial infarction. Am J Obstet
Gynecol 1981; 139- 47-51.
[74] Ness R, Schotland H, Flegal K et al. Reproductive history and
coronary heart disease risk in women. Epidemiologic Reviews,
16, 2, 298-312. The Johns Hopkins University School of
Hygiene and Public Health.